Nanowire Biosensor Research Articles

Investigation of Size Dependence on Sensitivity for Nanowire FET Biosensors

Label-free electrical detection of biomolecules is demonstrated with a double-gate (DG) nanowire (NW) field-effect transistor (FET). Experimental results confirm that detection sensitivity is favorably improved by the increment of NW size in the DG-NWFET, whereas it is enhanced by the decrement of NW size in a conventional single-gate (SG) NWFET. Sensitivity improvement by the augmentation of the NW size in the DG-FET paves the way to overcome technical challenges we face in achieving ultimate miniaturization of the NW size in the SG-FET. This result is comprehensively understood by simple capacitive modeling. The proposed model explains the observed experimental data and provides a design guideline for highly sensitive NW biosensors.

The α-Si/SiGe Core/Shell Nano-Wire as Highly Sensitive Bio-Sensor

Reducing the width of a nano-wire increases its surface to volume ratio, increasing the sensitivity of its conductivity to charges on its surface. Our previous studies have shown that increasing the Ge fraction in Si1-xGex nano-wires improves their sensitivity as bio-sensing. In this work, an α-Si/SiGe core/shell nano-wire is successfully fabricated using side-wall spacer method. The maximum sensitivity of a nano-wire bio-sensor with an optimizedα-Si/SiGe thickness ratio is investigated.

Highly sensitive single polyaniline nanowire biosensor for the detection of immunoglobulin G and myoglobin

A single polyaniline (PANI) nanowire-based biosensor was established to detect immunoglobulin G (IgG) and myoglobin (Myo), which is one of the cardiac biomarkers. The single PANI nanowires were fabricated via an electrochemical growth method, in which single nanowires were formed between a pair of patterned electrodes. The single PANI nanowires were functionalized with monoclonal antibodies (mAbs) of IgG or Myo via a surface immobilization method, using 1-ethyl-3-(3-dimethyaminopropyl) carbodiimide (EDC), and N-hydroxysuccinimde (NHS). The functionalization was then verified by Raman spectroscopy and fluorescence microscopy. The target proteins of IgG and Myo were detected by measuring the conductance change of functionalized single PANI nanowires owing to the capturing of target proteins by mAbs. The detection limit was found to be 3 ng/mL for IgG and 1.4 ng/mL for Myo. No response was observed when single nanowires were exposed to a non-specific protein, demonstrating excellent specificity to expected target detection. Together with the fast response time (a few seconds), high sensitivity, and good specificity, this single PANI nanowire-based biosensor shows great promise in the detection of cardiac markers and other proteins.

From Nanostructure to Nano Biosensor: Institute of Nano Electronic Engineering (INEE), UniMAP Experience

Nanostructure is defined as something that has a physical dimension smaller than 100 nanometers, ranging from clusters and/or to dimensional layers of atoms. There are three most important nanostructures that are extensively studied and researched in various organizations including Institute of Nano Electronic Engineering (INEE) in UniMAP. These include quantum dot, nanowire, and nanogap, which have been successfully designed and fabricated using in-house facilities available. These are subsequently used as a main sensing component in nanostructures based biosensor. This fabrication, characterization and testing job were done within four main interlinked laboratories namely microfabrication cleanroom, nanofabrication cleanroom, failure analysis laboratory and nano biochip laboratory. Currently, development of Nano Biosensor is the main research focus in INEE. In principle, biosensor is an analytical device which converts a biological response into an electrical signal. Keywords: Nanostructure, INEE , nanowire , nanogap and Nano Biosensor

An algorithm for three-dimensional Monte-Carlo simulation of charge distribution at biofunctionalized surfaces

In this work, a Monte-Carlo algorithm in the constant-voltage ensemble for the calculation of 3d charge concentrations at charged surfaces functionalized with biomolecules is presented. The motivation for this work is the theoretical understanding of biofunctionalized surfaces in nanowire field-effect biosensors (BioFETs). This work provides the simulation capability for the boundary layer that is crucial in the detection mechanism of these sensors; slight changes in the charge concentration in the boundary layer upon binding of analyte molecules modulate the conductance of nanowire transducers. The simulation of biofunctionalized surfaces poses special requirements on the Monte-Carlo simulations and these are addressed by the algorithm. The constant-voltage ensemble enables us to include the right boundary conditions; the dna strands can be rotated with respect to the surface; and several molecules can be placed in a single simulation box to achieve good statistics in the case of low ionic concentrations relevant in experiments. Simulation results are presented for the leading example of surfaces functionalized with pna and with single- and double-stranded dna in a sodium-chloride electrolyte. These quantitative results make it possible to quantify the screening of the biomolecule charge due to the counter-ions around the biomolecules and the electrical double layer. The resulting concentration profiles show a three-layer structure and non-trivial interactions between the electric double layer and the counter-ions. The numerical results are also important as a reference for the development of simpler screening models.

Silicon Nanowire as Virus Sensor in a Total Analysis System

Silicon nanowires are very promising candidates for the sensitive detection of viruses or even early detection of cancer. Due to their small dimensions the attachment of even one particle on their surface leads to detectable changes in their conductivity. In this paper we describe the development (fabrication and testing) of a silicon nanowire biosensor equipped with microfludic channels and automatized data aquisition for the detection of antibodies against a small virus (Aleutian Disease Virus) causing plasmacytosis on mink and ferrets.

Label-Free, Electrical Biomarker Detection Based on Nanowire Biosensors Utilizing Antibody Mimics as Capture Probes

ABSTRACTAntibody mimic proteins (AMPs) are poly-peptides that bind to their target analytes with high affinity and specificity, just like conventional antibodies, but are much smaller in size (2-5 nm, less than 10kDa). In this report, we describe the first application of AMP in the field of nanobiosensors. In2O3 nanowire based biosensors have been configured with an AMP (Fibronectin, Fn) to detect nucleocapsid (N) protein, a biomarker for severe acute respiratory syndrome (SARS). Using these devices, N protein was detected at sub-nanomolar concentration in the presence of 44 μM bovine serum albumin as a background. Furthermore, negative control experiment is carried out to confirm the role of AMPs in N protein detection.

Self-assembled monolayer-assisted silicon nanowire biosensor for detection of protein–DNA interactions in nuclear extracts from breast cancer cell

The large number of estrogen receptor (ER) binding sites of various sequence patterns requires a sensitive detection to differentiate between subtle differences in ER–DNA binding affinities. A self-assembled monolayer (SAM)-assisted silicon nanowire (SiNW) biosensor for specific and highly sensitive detection of protein–DNA interactions, remarkably in nuclear extracts prepared from breast cancer cells, is presented. As a typical model, estrogen receptor element (ERE, dsDNA) and estrogen receptor alpha (ERα, protein) binding was adopted in the work. The SiNW surface was coated with a vinyl-terminated SAM, and the termination of the surface was changed to carboxylic acid via oxidation. DNA modified with amine group was subsequently immobilized on the SiNW surface. Protein–DNA binding was finally investigated by the functionalized SiNW biosensor. X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) were employed to characterize the stepwise functionalization of the SAM and DNA on bare silicon surface, and to visualize protein–DNA binding on the SiNW surface, respectively. We observed that ERα had high sequence specificity to the SiNW biosensor which was functionalized with three different EREs including wild-type, mutant and scrambled DNA sequences. We also demonstrate that the specific DNA-functionalized SiNW biosensor was capable of detecting ERα as low as 10 fM. Impressively, the developed SiNW biosensor was able to detect ERα–DNA interactions in nuclear extracts from breast cancer cells. The SAM-assisted SiNW biosensor, as a label-free and highly sensitive tool, shows a potential in studying protein–DNA interactions.

Calculation of Fluctuations in Boundary Layers of Nanowire Field-Effect Biosensors

Fluctuations in the biofunctionalized boundary layers of nanowire field-effect biosensors are investigated by using the stochastic linearized Poisson-Boltzmann equation. The noise and fluctuations considered here are due to the Brownian motion of the biomolecules in the boundary layer, i.e., the various orientations of the molecules with respect to the surface are associated with their probabilities. The probabilities of the orientations are calculated using their free energy. The fluctuations in the charge distribution give rise to fluctuations in the electrostatic potential and hence in the current through the semiconductor transducer of the sensor, both of which are calculated. A homogenization result for the variance and covariance of the electrostatic potential is presented. In the numerical simulations, a cross section of a silicon nanowire on a flat surface including electrode and back-gate contacts is considered. The biofunctionalized boundary layer contains single-stranded or double-stranded DNA oligomers, and varying values of the surface charge, of the oligomer length, and of the electrolyte ionic strength are investigated.

All-(111) Surface Silicon Nanowires: Selective Functionalization for Biosensing Applications

We demonstrate the utilization of selective functionalization of carbon-silicon (C-Si) alkyl and alkenyl monolayers covalently linked to all-(111) surface silicon nanowire (Si-NW) biosensors. Terminal amine groups on the functional monolayer surfaces were used for conjugation of biotin n-hydroxysuccinimide ester. The selective functionalization is demonstrated by contact angle, X-ray photoelectron spectroscopy (XPS), and high-resolution scanning electron microscopy (HRSEM) of 5 nm diameter thiolated Au nanoparticles linked with streptavidin and conjugated to the biotinylated all-(111) surface Si-NWs. Electrical measurements of monolayer passivated Si-NWs show improved device behavior and performance. Furthermore, an analytical model is presented to demonstrate the improvement in detection sensitivity of the alkyl and alkenyl passivated all-(111) Si-NW biosensors compared to conventional nanowire biosensor geometries and silicon dioxide passivation layers as well as interface design and electrical biasing guidelines for depletion-mode sensors.

Probing the sensitivity of nanowire-based biosensors using liquid-gating

We have used liquid-gating to investigate the sensitivity of nanowire (NW)-basedbiosensors for application in the field of ultrasensitive biodetection. Wedeveloped an equivalent capacitance model of the biosensor system toexplore the dependence of the sensitivity on the liquid-gate voltage (Vlg), which was influenced by capacitive competition between the NW capacitance and thethin oxide capacitance. NW biosensors with highest sensitivity were obtained when weoperated the device in the subthreshold regime while applying an appropriate value ofVlg; the influence of leakage paths through the ionic solutions led, however, to significantsensitivity degradation and narrowed the operating window in the subthreshold regime.

Highly sensitive and reversible silicon nanowire biosensor to study nuclear hormone receptor protein and response element DNA interactions

To thoroughly understand the role that estrogen receptors partake in regulation of gene expression, characterization of estrogen receptors (ERs) and estrogen-response elements (EREs) interactions is essential. In the work, we present a highly sensitive and reusable silicon nanowire (SiNW) biosensor to study the interactions between human ER proteins (ER, α and β subtypes) and EREs (dsDNA). The proteins were covalently immobilized on the SiNW surface. Various EREs including wild-type, mutant and scrambled DNA sequences were then applied to the protein-functionalized SiNW surface. Due to negatively charged dsDNA, binding of the EREs to the ERs on the n-type SiNW biosensor leads to the accumulation of negative charges on the surface, thereby inducing increase in resistance. The results show that the specificity of the ERE–ERα binding is higher than that of the ERE–ERβ binding, what is more, the mutant ERE reduces the binding affinity for both ERα and ERβ. By applying various concentrations of wild-type ERE to the bound ERα, a very low concentration of 10 fM wild-type ERE was found to be able to bind to the ERα. The reversible association and dissociation between ERα and wt-ERE was achieved, pointing to a reusable biosensor for protein–DNA binding. Through the study, we have established the SiNW biosensor as a promising method in providing comprehensive study for hormone receptor–response element interactions.

Polypyrrole nanowire modified with Gly-Gly-His tripeptide for electrochemical detection of copper ion

We developed a novel biosensor comprising a transducer of carboxyl end-capped overoxidized polypyrrole nanowire electrode and a probe of tripeptide (Gly-Gly-His) selectively cognitive of Cu 2+. The developed sensor was demonstrated to specifically detect Cu 2+ in the nanomolar range. The diameter of the polypyrrole nanowires, prepared by one step template-free polymerization, was approximately 60–90 nm. For functionalization of the electrode, the carboxyl group was introduced by the addition of pyrrole-α-carboxylic acid which was covalently coupled with the amine group of the tripeptide. The structural features of the peptide functionalized nanowire electrode were confirmed by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) spectroscopy. Using cyclic and square wave voltammetry, the nanowire biosensor proved to be highly sensitive to Cu 2+ in the range of 20–300 nM.

ZnO nanowire biosensors for detection of biomolecular interactions in enhancement mode

One-dimensional oxide semiconductors have two main advantages for use in biosensors: oxide stable surfaces and high surface-to-volume ratios. In this paper, we describe a ZnO nanowire (NW) field effect transistor (FET) based biosensor for the detection of low level biomolecular interactions. ZnO NWs were grown on Au-coated Al 2O 3 (0 0 0 1) substrates by using pulsed laser (PL) deposition in an alumina tube placed inside a furnace. Field emission scanning electron microscopy (FE-SEM) images indicate that the average diameters of the ZnO NWs were about 70 nm, and that the average length was about 8 μm. The well-crystallized structural quality of the ZnO NW was examined using photoluminescence (PL) emission measurement. The ZnO NW biosensor functionalized with biotin can easily detect streptavidin binding. The binding of streptavidin with the concentrations from 0 to 250 nM resulted in the electrical current changes of up to 22.5 nA. The ZnO NW biosensor could detect as low as 2.5 nM of the streptavidin with 7.5 nA of current increase, which implied that the sensitivity of the biosensor can be below the nM concentration of biomolecules. This novel ZnO NW biosensor has potential for sensitive, label-free, and real time detection of a wide range of biological species.

Morpholino-functionalized silicon nanowire biosensor for sequence-specific label-free detection of DNA

We investigated Morpholino-functionalized silicon nanowires (SiNWs) as a novel gene chip platform for the sequence-specific label-free detection of DNA. Morpholino attachment and subsequent Morpholino–DNA hybridization on silicon surface was characterized by X-ray photoelectron spectroscopy and fluorescence microscopy. The resultant Morpholino-modified surfaces showed high specificity of recognition for DNA. Subsequently, by using the same protocol, the surface of the SiNW biosensor was functionalized with Morpholino, and this was used for label-free Morpholino-DNA hybridization detection. Real-time measurements of the Morpholino-functionalized SiNW biosensor exhibited a decrease in a time-dependent conductance when complementary and mutant DNA samples were added. Furthermore, identification of fully complementary versus mismatched DNA samples was carried out by the Morpholino-functionalized SiNW biosensor. We demonstrated that DNA detection using the Morpholino-functionalized SiNW biosensor could be carried out to the hundreds of femtomolar range. The Morpholino-functionalized SiNWs show a novel biosensor for label-free and direct detection of DNA with good selectivity, and a promising application in gene expression.

Fabrication and application of a microfluidic‐embedded silicon nanowire biosensor chip

AbstractWe report the fabrication of a silicon nanowire (SiNW) transistor array realized in a top‐down process on 4′′ silicon‐on‐insulator (SOI) wafers. This process is a second, optimized version combining thermal nanoimprint lithography and wet chemical etching to define planar nanowires and contact lines out of the top silicon layer in one etching step. We used ion implantation to reduce series resistance of source and drain contact lines. In total 56 individually addressable SiNWs were aligned in two lines. Wires dimensions were down to 60 nm in width and 40 nm in height having lengths up to 40 µm. Due to an improved processing we obtained almost identical wire structures and electronic properties throughout the 4′′ wafer enabling direct comparison of signals from one chip. The wires were capped by a microfuidic structure, which was used to administer different analyte solutions. First pH characterization measurements and molecular detection experiments using charged polyelectrolytes (PEs) and poly(D)lysine were successful. In future these devices could be used to observe diffusion of analytes in a time‐dependent, spatially‐ and quantitatively‐resolved readout.

One-dimensional nanostructures for electronic and optoelectronic devices

One-dimensional (1-D) nanostructures have been the focus of current researches due to their unique physical properties and potential applications in nanoscale electronics and optoelectronics. They address and overcome the physical and economic limits of current microelectronic industry and will lead to reduced power consumption and largely increased device speed in next generation electronics and optoelectronics. This paper reviews the recent development on the device applications of 1-D nanostructures in electronics and optoelectronics. First, typical 1-D nanostructure forms, including nanorods, nanowires, nanotubes, nanobelts, and hetero-nanowires, synthesized from different methods are briefly discussed. Then, some nanoscale electronic and optoelectronic devices built on 1-D nanostructures are presented, including field-effect transistors (FETs), p-n diodes, ultraviolet (UV) detectors, light-emitting diodes (LEDs), nanolasers, integrated nanodevices, single nanowire solar cells, chemical sensors, biosensors, and nanogenerators. We then finalize the paper with some perspectives and outlook towards the fast-growing topics.

Electrical detection-based analytic biodevice technology

Numerous traditional detection technologies such as fluorescence-based methods and enzymelinked immune-sorbent assay (ELISA) have been evaluated for the measurement of biological binding events. However, conventional detection methods are unsuitable for miniaturization and are unsatisfactory candidates for integration into hand-held sensors. Thus, electrical detection of biological binding events, such as protein-protein interaction and DNA hybridization, has emerged as an alternative method to currently used colorimetric and fluorescence-based methods. Due to its response time, cost effectiveness, high sensitivity, and ease of integration with semiconductor technology, the demand for this technology is increasing. This article reviews electrical detection systems focusing on electrical detection-based nanowire biosensors, protein chip based on electrical detection systems, and cell chip based on electrochemical detection methods.

Multiscale Modeling of Planar and Nanowire Field-Effect Biosensors

Field-effect nanobiosensors (or Biofets, biologically sensitive field-effect transistors) have recently been demonstrated experimentally and have thus gained interest as a technology for direct, label-free, real-time, and highly sensitive detection of biomolecules. The experiments have not been accompanied by a quantitative understanding of the underlying detection mechanism. The modeling of field-effect biosensors poses a multiscale problem due to the different length scales in the sensors: the charge distribution and the electric potential of the biofunctionalized surface layer changes on the Ångström length scale, whereas the exposed sensor area is measured in micrometers squared. Here a multiscale model for the electrostatics of planar and nanowire field-effect sensors is developed by homogenization of the Poisson equation in the biofunctionalized boundary layer. The resulting interface conditions depend on the surface charge density and dipole moment density of the boundary layer. The multiscale model can be coupled to any charge transport model and hence makes the self-consistent quantitative investigation of the physics of field-effect sensors possible. Numerical verifications of the multiscale model are given. Furthermore a silicon nanowire biosensor is simulated to elucidate the influence of the surface charge density and the dipole moment density on the conductance of the semiconductor transducer. The numerical evidence shows that the conductance varies exponentially as a function of both charge and dipole moment. Therefore the dipole moment of the surface layer must be included in biosensor models. The conductance variations observed in experiments can be explained by the field effect, and they can be caused by a change in dipole moment alone.

A Calibration Method for Nanowire Biosensors to Suppress Device-to-Device Variation

Nanowire/nanotube biosensors have stimulated significant interest; however, the inevitable device-to-device variation in the biosensor performance remains a great challenge. We have developed an analytical method to calibrate nanowire biosensor responses that can suppress the device-to-device variation in sensing response significantly. The method is based on our discovery of a strong correlation between the biosensor gate dependence (dI(ds)/dV(g)) and the absolute response (absolute change in current, DeltaI). In(2)O(3) nanowire-based biosensors for streptavidin detection were used as the model system. Studying the liquid gate effect and ionic concentration dependence of strepavidin sensing indicates that electrostatic interaction is the dominant mechanism for sensing response. Based on this sensing mechanism and transistor physics, a linear correlation between the absolute sensor response (DeltaI) and the gate dependence (dI(ds)/dV(g)) is predicted and confirmed experimentally. Using this correlation, a calibration method was developed where the absolute response is divided by dI(ds)/dV(g) for each device, and the calibrated responses from different devices behaved almost identically. Compared to the common normalization method (normalization of the conductance/resistance/current by the initial value), this calibration method was proven advantageous using a conventional transistor model. The method presented here substantially suppresses device-to-device variation, allowing the use of nanosensors in large arrays.